Thalamocortical network neuromodulation for epilepsy

Objectives Despite the growing interest in network-guided neuromodulation for epilepsy, uncertainty about the safety and long-term efficacy of thalamocortical stimulation persist. Our evaluation focused on the use of a 4-lead open-loop implantable pulse generator (IPG) for thalamocortical network neuromodulation. Methods We retrospectively reviewed seven subjects with diverse seizure networks (SNs)—poorly localized, regional, or multifocal—undergoing thalamocortical neuromodulation. Employing a 4-lead system, electrodes targeted both thalamic and cortical SN nodes. We assessed seizure severity, life satisfaction, and sleep quality on a 10-point scale, and seizure frequency via telephone interviews and chart review. Six subjects underwent open-loop stimulation trials during intracranial EEG (iEEG) to confirm SN engagement and optimize settings, targeting the suppression of interictal epileptiform discharges (IEDs) and seizures. Outcomes were assessed by Wilcoxon sign-rank test, 0.05 significance level. Results After a median of 17 months post-implantation (range 13–60), subjects had a median disabling seizure reduction of 93% (range 50-100%, p=0.0156), with 100% responder rate (≥50% reduction in seizure frequency). The median improvement in seizure severity was 3.5 out of 10 points (p=0.0312), life satisfaction 4.5 points (p= 0.0312), and quality of sleep 3 points (p=0.062). No perioperative complications occurred. Rare transient seizure exacerbations and stimulation-related sensory/motor side effects resolved with parameter adjustments. One subject required surgical revision due to delayed infection. Six subjects had permanent electrode placement refined by iEEG trial stimulation; five subjects had >90% reduction in seizure frequency during iEEG stimulation. Significance Thalamocortical network neuromodulation using a 4-lead open-loop system is safe, and is associated with significant improvements in seizure control and patient quality of life. Trial stimulation during iEEG shows promise for enhancing SN engagement and parameter optimization, but requires further study. Prospective controlled trials are needed to establish the validity of thalamocortical network neuromodulation for epilepsy. Key Points Thalamocortical neuromodulation with a 4-lead open-loop stimulation system is feasible and safe, and is associated with significant improvements in seizure control and life satisfaction. Trials of therapeutic stimulation during phase 2 iEEG monitoring has the potential to refine seizure network engagement and optimize stimulation parameters, for more effective chronic neuromodulation. Prospective controlled trials are needed to validate the efficacy of thalamocortical network neuromodulation.